Is there any evidence that deconditioning alone causes pain and fatigue?

Good work oceanblue. Did these studies account for differences in cognitive activity during bed rest? I do not think the CBM proponents attribute all the subjective cognitive difficulties in CFS to physical deconditioning, but also mental deconditioning (as well as other factors such as anxiety and sleep / circadian rhythm disturbances.

The PACE manuals claim that:

"Prolonged rest deprives people of intellectual stimulation and has a dulling effect on intellectual activity. [...] Excessive rest may even affect the way our brain cells make connections with each other. [...] This may impair concentration, memory, and the ability to find the correct word. [...] GET has been shown to improve mental functioning."

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Generally cognitive activity is unrestricted in bed rest studies. Did PACE offer any decent evidence to back up their bold claims? 'Mental deconditioning' is a new one to me, so thanks for that info. I should stress I'm not using decon evidence to debunk all of CBT, just the parts of it that rely on decon, which don't appear to be backed up by published evidence.

Generally cognitive activity is unrestricted in bed rest studies. Did PACE offer any decent evidence to back up their bold claims? 'Mental deconditioning' is a new one to me, so thanks for that info. I should stress I'm not using decon evidence to debunk all of CBT, just the parts of it that rely on decon, which don't appear to be backed up by published evidence.

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The information I quoted was from both the CBT participant and GET participant manuals. I just had a quick look for references, but could not find any in either manual (neither inline citations nor a list of references at the end). In general, there is a list of references at the end of the therapist versions of the CBT and GET manuals. The GET therapist manual even states on p78 that when participants ask for further references or suggested websites:

PACE said:

Explain that there are no particular references you can recommend for GET, but that you would be happy to make comment on anything they find. You should explain that there is a significant amount of inaccurate information on the internet, and in other publications, and that they need to approach this with caution.

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There is a section titled "Physiological aspects of CFS/ME" on p9-13 of the CBT participant manual and p13-20 of the GET participant manual, where I pulled the quotes for my previous post. The wording of the two versions are occasionally different (GET focuses more on physiology), but I have looked at this before so it will not be too much trouble to post notes I have made on an amalgamated version. I will only include the deconditioning related information here, but note that only the GET version mentions GET as the solution.

PACE said:

Over time, reduced or irregular activity and increased periods of rest causes physical changes in the body. These changes cause unpleasant sensations and symptoms that can be very distressing. It is important to point out that these changes are reversible with physical rehabilitation and/or (graded) exercise. Research has looked at the effects of rest in healthy people when they reduce their activities and many similarities between people with CFS/ME and healthy inactive people have been noted. The following information describes the effects of prolonged periods of inactivity on the body:-

1. Changes in muscle function

A decrease in the number of active cell mitochondria (tiny parts of the cell that act as an energy powerhouse) and their enzymes have been found in the muscles of people with CFS/ME when compared with healthy active people. The reduction of cell mitochondria has also been found in healthy inactive people. Fewer cell mitochondria may lead to production of lactic acid at low exercise levels, which in turn limits muscle performance. These changes may account for the feeling of a lack of power or energy in the muscles and stiffness after normal exercise and activity.

As reduced activity leads to less efficient muscles (reduced strength, tone and size), it is more difficult for the muscles to squeeze the blood back to the heart causing blood to pool in the lower part of the legs. Pooling of blood can cause pain and a feeling of heaviness both during activity and rest.

When muscles are not used regularly, they become weaker or unfit/deconditioned. One week of rest reduces strength in large muscles by 10%. When these muscles contract during activity, uneven stresses are produced. This may result in a feeling of weakness and instability/unsteadiness followed by delayed pain and discomfort.

However in all individuals, muscle pain and stiffness are a natural consequence and normal response to the beginning a new exercise programme or when unaccustomed physical activity or exercise is taken.

GET can help by building muscle strength, which in turn allows you to do more.

2. Changes in the cardiovascular system

The cardiovascular system (which incorporates the heart and blood vessels) becomes out of condition very quickly with rest. The longer you rest, the more changes occur.

Physical changes that occur with cardiovascular deconditioning include:
• reduced blood volume after 1 or 2 days bed-rest,
• reduced volume of red blood cells after 8 days bed-rest which reduces oxygen carrying capacity of the blood,
• volume of the heart reduces by about 15% after 20 days of bed-rest therefore less blood is pumped to other organs,
• when standing it is more difficult to maintain a normal blood pressure.

These physical changes may result in making you feel breathless or dizzy when exercising or undertaking physical activity, and contribute to your fatigue. The reduced blood flow to the brain causes dizziness and sometimes fainting. Following a "lying down" rest there is a drop in blood pressure on standing up (postural hypotension) due to blood pooling in the legs. Consequently, less blood returns to the heart and therefore less blood goes to the brain causing these symptoms.

GET can help by improving fitness and the efficiency of your cardiovascular system.

3. Regulation of body temperature

<omitted>

4. Visual and hearing changes

Prolonged bed-rest results in a “headward” shift of bodily fluids and a change in the way the brain perceives external sensations, like noise and light, with consequent sensitivity. This may result in visual problems and sensitivity to noise.

5. Reduced tolerance to activity or exercise

General weakening/de-conditioning of the body occurs as a result of prolonged rest or reduced activity.

[CBT version: This results in being less able to tolerate activity as fitness reduces. Muscle fatigue and feelings of heaviness as well as a general increase in overall fatigue occurs when active.]

[GET version: This results in being less able to tolerate activity as fitness and muscle strength reduces. Fatigue, pain and heaviness in the muscles can result, as can an overall sense of bodily fatigue.]

GET can help by improving your ability to undertake physical activities.

6. Changes in the nervous system

One of the functions of the nervous system is to co-ordinate our muscles. Regular performance of an activity is required to maintain good co-ordination. Prolonged periods of inactivity therefore reduce our co-ordination. This may result in unsteadiness, clumsiness and reduced accuracy when carrying out precise movements.

GET can help by challenging your body physically, which can lead to improved coordination and balance.

7. Changes in mental functioning

Prolonged rest deprives people of intellectual stimulation and has a dulling effect on intellectual activity. Excessive rest may even affect the way our brain cells make connections with each other. This may impair concentration, memory, and the ability to find the correct word.

GET has been shown to improve mental functioning.

8. Alteration of the biological clock

<omitted>

9. Disturbance of cortisol production

<omitted>

10. Disturbance of the sleep-wake rhythm in CFS/ME

<omitted>

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The section on "Autonomic arousal in CFS/ME" (p14-16 of the CBT participant manual and p21-24 of the GET participant manual) discusses the physical and mental effects of anxiety/stress/perceived-threats. Furthermore, it alludes that autonomic arousal can help to explain post-exertional symptoms:

PACE said:

During periods of prolonged physical or mental exertion, there is increased activity of the nervous systems and increased adrenaline production. This leads to symptoms similar to those experienced in a flu-like illness, such as aches and pains, headache, sweating, feeling hot and cold, chest tightness and sore throat. If a person experiences these symptoms after activity, they may reduce or avoid activities, as they may believe that they are coming down with flu or a cold. Limiting activity can perpetuate the physical effects of anxiety and lead to a further reduction of fitness and muscle strength.

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The GET version adds: "The autonomic response is your body's way of preparing you for action. However, if you don't take physical action, symptoms can result. You can therefore use GET as a way of dealing constructively with this response."

IIRC, Powell's "Liverpool CF/CFS clinic handout", which PACE acknowledges was used in their manuals, also mentions that deconditioning either increases autonomic arousal or increases the autonomic response to exertion? As a finishing side note to my previous post, mental functioning is also discussed in the above sections on autonomic arousal, alteration of the biological clock, disturbance of cortisol production, and disturbance of the sleep-wake rhythm.[/b]

The information I quoted was from both the CBT participant and GET participant manuals. I just had a quick look for references, but could not find any in either manual (neither inline citations nor a list of references at the end).

EDIT: from PACE manuals:
Research has looked at the effects of rest in healthy people when they reduce their activities and many similarities between people with CFS/ME and healthy inactive people have been noted.

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Thanks for such impressive and helpful quotes & notes.

So, they did use the argument of the effect on inactivity on healthy individuals, but cherry-picked or mis-represented the evidence, or just merely speculated wildly to back up their hypothesis. Now that I'm a bit more familiar with the bed rest and other literature it's a bit easier to see the sleight of hand. Here's a rebuttal to some of the quotes you highlighted.

"Over time, reduced or irregular activity and increased periods of rest causes physical changes in the body"...Reality: this bit is absolutely right, there is extensive evidence that bed rest leads to numerous measurable physiological changes.

"These changes cause unpleasant sensations and symptoms [that can be very distressing]"...Reality: However, there is surprisingly little, if any, evidence for CFS-like symptoms in bed rest studies. In fact I was struck by how little mention there was of physical fatigue, pain, mental fatigue or cognitive problems. This omission is particularly striking as most bed rest studies on healthy individuals were carried out for US and Russian Space programmes, specifically to look at any negative effects of microgravity* on the ability of astronauts to function. And CFS is defined by it's serious impact on ability to function; if you had these symptoms, you would notice.[* Bed Rest has been shown to be the best available long-term proxy for microgravity in Earth-bound studies]

"It is important to point out that these changes are reversible with physical rehabilitation and/or (graded) exercise."Reality: Yes, the changes brought on in healthy adults by bed rest are reversible with physical rehabilitation, but these changes don't include CFS-like symptoms

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"1. Changes in muscle function
.... As reduced activity leads to less efficient muscles (reduced strength, tone and size), it is more difficult for the muscles to squeeze the blood back to the heart causing blood to pool in the lower part of the legs. Pooling of blood can cause pain and a feeling of heaviness both during activity and rest."Reality: No evidence at all in bed rest studies of pain; some of heaviness but only briefly after longer-term bed rest and this only lasted a few days. There is no evidence that such pooling is happening in CFS patients, or that it is responsible for pain/heaviness.

"When muscles are not used regularly, they become weaker or unfit/deconditioned. One week of rest reduces strength in large muscles by 10%. When these muscles contract during activity, uneven stresses are produced. This may result in a feeling of weakness and instability/unsteadiness followed by delayed pain and discomfort."Reality: Studies have found that after 3 months (13 weeks) of bed rest, fitness declines by only a third, and that's far more resting than is typical for CFS patients in outpatient clinics. There's no evidence that the 'low-normal' levels of fitness in CFS patients could account for such weakness/delayed pain and discomfort.

Claim: "However in all individuals, muscle pain and stiffness are a natural consequence and normal response to the beginning a new exercise programme or when unaccustomed physical activity or exercise is taken."Reality: yes, we know that and are familiar with it; PEM is something else altogether.

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"2. Changes in the cardiovascular system

The cardiovascular system (which incorporates the heart and blood vessels) becomes out of condition very quickly with rest. The longer you rest, the more changes occur.Reality: Although this is broadly true, the changes in the cardiovascular system are more dramatic than the changes in fitness levels, which is the key issue here.

These physical changes may result in making you feel breathless or dizzy when exercising or undertaking physical activity, and contribute to your fatigue.Reality: No evidence for this in bed rest studies, apart from those of 6 months or more which hardly apply to the CFS patients seen as outpatients. And no evidence at all that deconditioning driven by inactivity causes these symptoms in CFS.

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The consistent approach here seems to be come up with an idea that seems plausible eg inactivity causes deconditioning which leads to all sorts of symptoms, either at rest or when attempting activity, and make a leap of faith that this explains much of CFS. The evidence offered is weak, indirect and cherry-picked - where it exists at all.

I could go on in the same vein about the rest of their evidence, but don't see the point...

Their willingness to do this as part of attempt to 'manage' patients from a position of medical authority is pretty sickening. "It may be that... alien organisms grown by the government and implanted in to specific members of the public are causing you CFS". That is true, but...

Prolonged rest deprives people of intellectual stimulation and has a dulling effect on intellectual activity. Excessive rest may even affect the way our brain cells make connections with each other. This may impair concentration, memory, and the ability to find the correct word.Reality: Without references, it's hard to know what they are talking about, but I've never come across any evidence for this. Have I missed something, or is this an example of @Esther12's Aliens? More to the point, I wasn't aware that most CFS patients were even assumed to excessively avoid intellectual activity. Obviously doesn't apply to anyone on this forum...

Actually, I did find one paper making the same link between GET helping mental functioning (a bit) in healthy adults, therefore deconditioning must do the opposite, citing the reference I've linked to in the previous paragraph, but no hard evidence for it. That's quite common in the deconditioning literature; start from a theory and assume it's true without doing the experiment.

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The section on "Autonomic arousal in CFS/ME" (p14-16 of the CBT participant manual and p21-24 of the GET participant manual) discusses the physical and mental effects of anxiety/stress/perceived-threats. Furthermore, it alludes that autonomic arousal can help to explain post-exertional symptoms:

PACE said:

During periods of prolonged physical or mental exertion, there is increased activity of the nervous systems and increased adrenaline production. This leads to symptoms similar to those experienced in a flu-like illness, such as aches and pains, headache, sweating, feeling hot and cold, chest tightness and sore throat. If a person experiences these symptoms after activity, they may reduce or avoid activities, as they may believe that they are coming down with flu or a cold. Limiting activity can perpetuate the physical effects of anxiety and lead to a further reduction of fitness and muscle strength.​

Reality: Well, personally I've never experienced flu-like symptoms after either physical or mental exertion when healthy - and at least when I was a student I did a lot of both. And I've never seen any research supporting this.

The GET version adds: "The autonomic response is your body's way of preparing you for action. However, if you don't take physical action, symptoms can result. You can therefore use GET as a way of dealing constructively with this response."Reality: This makes the leap of faith that GET works, which is the cart before the horse.

Explain that there are no particular references you can recommend for GET, but that you would be happy to make comment on anything they find. You should explain that there is a significant amount of inaccurate information on the internet, and in other publications, and that they need to approach this with caution.​

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Does anyone else find this in isolation an astonishing statement to put in such a manual. Since when was it appropriate to tell a patient that you can provide no supporting evidence for the treatment you are providing, it is up to them to find evidence against it, while simultaneously rubbishing all other sources. I know the NHS has a somewhat patronising view of patients but I have never seen anything this dismissive and would never accept such an attitude from my GP for example.

I accept that most patients would not generally ask for supporting evidence but surely if they do it is irresponsible not to provide it? This reads like the sort of get rich quackery that would normally quite rightly be derided by NHS practitioners - "just relax and trust me".

Jut to add I agree with all the citicisms here - and for all the reasons given. It's pretty obvious AFTER any illness and cure effected it's best to move about and regain muscle tone again. Doesn't everyone do it automatically without CBT or GET. More time spent on addressing the illness itself would only make this lot relevant for ME.

Extended bed rest may not have such a big impact on fitness (and function)[Capelli 2006]

I can't remember the exact figures quoted (Dolphin?) but I'm pretty sure proponents of the deconditioning model for CFS have stated that something like 30% of muscle mass is lost after 10 days in bed. The implication is that resting too much quickly leads to a spiral of lost function, more tiredness, more rest and so on.

However, when researchers have measured the effect of bed rest on healthy volunteers, using VO2max which is generally excepted as the best measure of fitness, they found it isn't that dramatic...

Effectively, as bed rest increases, the effect on VO2max declines i.e. fitness is lost more slowly as time goes on. A 27% loss of fitness after 3 months of complete round-the-clock bed rest is hardly spectacular, and the kind of CFS patients who make it to CFS outpatient clinics and studies won't be resting anything like as much as this.

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After 90 days of bed rest healthy volunteers are more deconditioned than CFS patients but less troubled by fatigue
Finally got hold of the full text, and I wanted to be sure that after 90 days of bed rest healthy volunteers were at least as deconditioned as CFS patients - there was some doubt as bed rest studies generally use very fit people.

So CFS patients before starting GET programmes are substantially fitter than people who have undergone bedrest for 3 months. In fact, as men should have VO2 max scores around 20% higher than women of the same age, the difference in fitness is even more striking. Yet as I've pointed out earlier in this thread, significant problems with fatigue are not reported after 3 months of bed rest either at rest or on reambulation.

A normal average VO2max for a group of ME-patients is 20 ml/kg/min, not 30. My own value is 15.

Most likely, nobody in that group has ME.

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As you'll see from earlier posts in this thread and based on the studies I've been able to find, there are range of values given for CFS (not seen any specifically for ME), but most are in the low normal range, like the one I quoted in my post above, which was from an outpatient clinic. Which studies did you have in mind for 20ml/kg/min?

Abstract
...
RESULTS:
Two thousand one hundred and thirty-seven episodes of absence due to infectious mononucleosis had a median duration of 91 days. Young employees (aged 15-24 years) had the highest return to work rates. Women had longer sickness absence than men...

CONCLUSIONS:Occupational physicians should advise gradual return to work, starting 4 weeks after the onset of the illness, in order to prevent physical deconditioning and prolonged illness.

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This study provides some interesting data on recovery rates from serologically-confirmed Infectious Mononucleosis on a large cohort with an objective outcome measure (full-time return to work).

However, the advice in the conclusion is unfounded and based on a misinterpretation of the literature, deliberate or otherwise. Essentially they are saying employees should be encouraged back to work regardless of how they feel, with this as the 'evidence':

In the literature, gradual return to competition is recommended for sportsmen with no spleen enlargement 4 weeks after the onset of illness [16,17]... Therefore, it should be feasible for employees to gradually return to work 4 weeks after the onset of sickness absence due to infectious mononucleosis.

No strong evidence-based information supports use of a single parameter to predict the safe return to sports participation. Current consensus supports that athletes be afebrile, well hydrated, and asymptomatic with no palpable liver or spleen.

it is generally felt that it is safe to resume light activity 3 weeks from the onset of symptoms, as long as the athlete is afebrile, has a good energy level, and does not have any significant associated abnormalities.

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In other words, the evidence for returning to activity is based on advice to athletes (they offer no evidence relating to non-athletes), which is not conclusive and stresses the need for being free of symptoms and having good energy levels.
Yet again there is a presumption that the problem with delayed recovery is due to physical deconditioning and therefore people should resume activity regardless - without any evidence backing up the presumption.

Still tidying up:

4. Visual and hearing changes
Prolonged bed-rest results in a “headward” shift of bodily fluids and a change in the way the brain perceives external sensations, like noise and light, with consequent sensitivity. This may result in visual problems and sensitivity to noise.

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Reality: I didn't find any references to these symptoms in any of the bed rest studies I found. Furthermore, most outpatients won't be affected by prolonged bed rest and headward shift of fluids, yet can still have problems with noise (I do) or light.

Thanks for this. It seems like a good idea to promote exercise as helpful, where it is appropriate, but there does seem to be a tendency to hype the results. A 2010 Cochrane reviewconcluded:

Exercise can be regarded as beneficial for individuals with cancer-related fatigue during and post cancer therapy. Further research is required to determine the optimal type, intensity and timing of an exercise intervention.

All patients getting cancer treatment should be told to do two and a half hours of [moderate intensity] physical exercise every week, says a report by Macmillan Cancer Support. Being advised to rest and take it easy after treatment is an outdated view, the charity says.

In the report, the American College of Sports Medicine also recommends that exercise is safe during and after most types of cancer treatment and says survivors should avoid inactivity.

"The evidence review shows that physical exercise does not increase fatigue during treatment, and can in fact boost energy after treatment."

"It can also lower their chances of getting heart disease and osteoporosis.

"Also, doing recommended levels of physical activity may reduce the chance of dying from the disease. It may also help reduce the risk of the cancer coming back."

"Cancer patients would be shocked if they knew just how much of a benefit physical activity could have on their recovery and long term health, in some cases reducing their chances of having to go through the gruelling ordeal of treatment all over again."

"But the evidence that exercise has a bearing on survival is not conclusive. It is important to remember that no two cancer patients are the same, so rehabilitation programmes that include physical activity will need to be tailored to the individual."

Damn it, CFS research has ruined my ability to take other research at face value! These statements about cancer could be as dubious as those made for exercise and CFS. Sounds like hyperbole to me, and the general popularity of bandying around correlation as causation has me cautious about the claimed longitudinal benefits. The several systematic reviews I've skimmed through (quick PubMed search plus oceanblue's post) don't seem to support the hype, although some benefits in multiple domains seem probable.

I wonder how many patients have gone to their doctor for ME/CFS and were told about the awesome unquestionable "wonder-drug type benefits" (The Telegraph) / magical powers of exercise to heal, due to the PACE Trial or reports on similar research. I myself have been told repeatedly about such wonderful effects, I "believed", but here I am years later struggling to climb one or two flights of stairs without leaning on the rails. I now know it was quackery.

It's also worth noting that the advice for exercising in cancer patients stresses the need to adapt the exercise to take account of symptoms resulting from the exercise.

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There are similar cautions in CBT/GET protocols, although there may be large variabilities in how much symptom exacerbation is tolerated in practice before adjustment, and in how much is just lip service given to tailor-babble.

I wonder how many patients have gone to their doctor for ME/CFS and were told about the awesome unquestionable "wonder-drug type benefits" (The Telegraph) / magical powers of exercise to heal, due to the PACE Trial or reports on similar research. I myself have been told repeatedly about such wonderful effects, I "believed", but here I am years later struggling to climb one or two flights of stairs without leaning on the rails. I now know it was quackery.

It's also worth noting that the advice for exercising in cancer patients stresses the need to adapt the exercise to take account of symptoms resulting from the exercise.

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There are similar cautions in CBT/GET protocols, although there may be large variabilities in how much symptom exacerbation is tolerated in practice before adjustment, and in how much is just lip service given to tailor-babble.

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I know, and this is a bit weird. PACE criticises pacing for being adaptive to the illness ie symptom-limited, while CBT/GET are more target driven - yet their manuals stress the need to adapt the programme to the illness.

It seems like a good idea to promote exercise as helpful, where it is appropriate, but there does seem to be a tendency to hype the results....
It's also worth noting that the advice for exercising in cancer patients stresses the need to adapt the exercise to take account of symptoms resulting from the exercise.

CFS research has ruined my ability to take other research at face value! These statements about cancer could be as dubious as those made for exercise and CFS. Sounds like hyperbole to me, and the general popularity of bandying around correlation as causation has me cautious about the claimed longitudinal benefits.

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unsurprisingly, these were my thoughts as well

I'm supposed to be working on something else, though, so didn't have time to look beyond the first of the dubious-appearing claims in the pdf and actually pull up some of the research.

It was relatively controlled alright. But the theory isn't that one "if there was a flare up after an incremental increase in activity, then the activity levels would be reduced." GET is about breaking that link.

You may be familiar with setbacks: in this context, we are referring to an increase in symptoms that occurs, usually after an increase in activity or for some other reason, that significantly affects your ability to undertake activity for as time-limited period. The cause, severity and duration of setbacks can be variable. [..]

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Dealing with a CFS/ME setback: what should I do?

During a CFE/ME setback, it is understandable that you might wish to rest and reduce the amount of activity you do, because you don’t feel well and activity feels much harder than usual. This may even be a time in which you become concerned that the increase in symptoms may be causing you damage.

The evidence we have is in fact the opposite: there is no evidence to suggest that an increase in symptoms is causing you harm. It is certainly uncomfortable and unpleasant, but not harmful....

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Not sure I have ever seen any evidence of this being put to the test. So there may be no published evidence of harm, but I'm not sure anyone has ever done the research to investigate this properly.

...[cont] Dealing with a CFS/ME setback: what should I do?In fact, there is much evidence to support the alternate view: if you rest too much, it is the resting that can cause negative changes in the body. Resting and withdrawing from activity can also make us feel fed up or worried, and this can also make it harder to continue being active.

The periods of excessive rest can be a time when the body adjusts to the lower level of activity and weakens: if the body weakens further, it can become more sensitive to activity and make overall symptoms worse.

Therefore, during a setback it is useful to maintain as much physical activity as you can. This is to avoid the weakening and tightening of muscles, and the reduction in fitness, which can occur surprisingly quickly (we can lose 10 % of our muscle strength in just one week of bed-rest, or even 1% per day). [...cont]

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Worth pointing out (see posts above) that while there is evidence of rapid muscle loss on bed rest, the loss of fitness - or work capability - is much slower, around 27% after 3 months, or 0.3% a day.

...[cont] Dealing with a CFS/ME setback: what should I do?
Therefore, if at all possible, try to keep to your exercise and activity plan, knowing that in time your body will adjust.

Of course, if you are having a very severe setback, in which your previous level of activity is leading to distressing or unmanageable symptoms, then reducing activity slightly and increasing rest might be a temporary solution, as long as you build up again as soon as you can to your previous level. Building up again should ideally occur within a few days to avoid the detrimental effects of rest. Reducing activity should be avoided if at all possible.

It can be helpful to use other strategies during a setback, such as muscle relaxation, or gentle stretches that can relieve discomfort. Warm baths can also help your muscles feel more comfortable. It is also useful to try to avoid extra sleeping where possible, as this can make it harder for you to get back into physical activity.